IJE Advance Access originally published online on March 11, 2004
International Journal of Epidemiology 2004 33(5):955-961; doi:10.1093/ije/dyh102
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IJE vol.33 no.5 © International Epidemiological Association 2004; all rights reserved.
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TGFß1 polymorphism (L10P) and risk of colorectal adenomatous and hyperplastic polyps
1 Fred Hutchinson Cancer Research Center, Seattle, Washington, 98109, USA
2 Department of Epidemiology, University of Washington, Seattle, Washington, 98195, USA
Correspondence: Cornelia Ulrich, Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M4-B402, Seattle, WA 98109–1024, USA. E-mail: nulrich{at}fhcrc.org
Background Transforming growth factor-ß1 (TGFb1) is a multifunctional signalling molecule with a wide array of roles. Animal experiments suggest that TGFb1 plays a biphasic role in carcinogenesis by protecting against the early formation of benign epithelial growths, but promoting malignant transformation of those growths that do develop. A polymorphism in the signal peptide sequence of the TGFß1 gene (L10P) has been associated with increased levels of plasma TGFb1 in individuals with the P allele.
Methods We investigated whether this polymorphism was associated with the risk of colorectal adenomatous or hyperplastic polyps in a case-control study of individuals from Minnesota. Risk of colorectal polyps was evaluated separately for individuals with adenomatous polyps (n = 513) and hyperplastic polyps (n = 191) relative to polyp-free controls (n = 606) using logistic regression analysis.
Results No overall association was seen between the L10P polymorphism and risk of colorectal adenomatous polyps. The age- and sex-adjusted odds ratios (OR) of developing colorectal hyperplastic polyps were 1.0 (95% CI: 0.7, 1.4) and 0.7 (95% CI: 0.4, 1.1) for individuals with the LP and PP genotypes, respectively, compared with individuals with the LL genotype. When stratified by smoking, evidence for a decreased risk of hyperplastic polyps associated with the P allele was seen only among ever smokers (P for trend = 0.05).
Conclusions Whereas adenoma risk did not vary by TGFß1 L10P genotype, these results suggest that the L10P variant allele may have a protective role in the development of colorectal hyperplastic polyps, possibly consistent with its role as an inhibitor of epithelial growths.
Keywords Colorectal cancer, colorectal adenoma, transforming growth factor beta, polymorphism, smoking, aspirin, non-steroidal anti-inflammatory drugs
Accepted 19 December 2003
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